Final Diagnosis
Nodular fasciitis.
Discussion
Nodular fasciitis is a benign, self-limited myofibroblastic neoplasm that classically presents as a rapidly growing superficial soft tissue mass, often raising clinical concern for sarcoma. It most commonly affects young to middle-aged adults and frequently arises in the upper extremities, trunk, and head and neck region. Lesions are usually small, typically measuring less than 3 cm, and may develop over only a few days or weeks. Historically regarded as a reactive process, nodular fasciitis is now recognized as a transient neoplasm driven by recurrent USP6 gene rearrangements.
Histologically, nodular fasciitis demonstrates a proliferation of bland fibroblastic and myofibroblastic spindle cells arranged in short fascicles within a myxoid to collagenous stroma. Characteristic features include a tissue-culture-like growth pattern, extravasated erythrocytes, microcystic change, and scattered inflammatory cells. Mitotic activity may be readily identified but atypical mitotic figures are absent. The lesion can appear infiltrative at the periphery and, when combined with its rapid growth and cellularity, may mimic a malignant spindle cell neoplasm.
Immunohistochemically, lesional cells frequently express SMA, supporting myofibroblastic differentiation, while S100 protein, cytokeratins, and CD34 are typically negative. Desmin can be focally positive. These findings are helpful in excluding other spindle cell lesions, although no immunophenotypic profile is entirely specific. Consequently, molecular confirmation has become an important adjunct in diagnostically challenging cases.
The discovery of recurrent USP6 rearrangements fundamentally changed the understanding of nodular fasciitis. The most common fusion partner is MYH9, although numerous alternative partners have been described. These promoter-swapping events result in USP6 overexpression and support the concept that nodular fasciitis represents a genetically driven but self-limited neoplasm. Break-apart FISH for USP6 is a valuable diagnostic tool, particularly in limited biopsies or cases with unusual morphology. The presence of a USP6 rearrangement strongly supports the diagnosis when interpreted in the appropriate morphologic and immunophenotypic context.
Complete local excision is curative in most cases, and recurrence is uncommon. Some lesions may regress spontaneously, further supporting their transient biological behavior. Recognition of the characteristic clinicopathologic features and appropriate use of molecular testing are essential to avoid overtreatment and misclassification as sarcoma.
Key References
- Erickson-Johnson, M. R., Chou, M. M., Evers, B. R., Roth, C. W., Seys, A. R., Jin, L., Ye, Y., Lau, A. W., Wang, X., & Oliveira, A. M. (2011). Nodular fasciitis: a novel model of transient neoplasia induced by MYH9-USP6 gene fusion. Laboratory investigation; a journal of technical methods and pathology, 91(10), 1427–1433. https://doi.org/10.1038/labinvest.2011.118
- Patel, N. R., Chrisinger, J. S. A., Demicco, E. G., Sarabia, S. F., Reuther, J., Kumar, E., Oliveira, A. M., Billings, S. D., Bovée, J. V. M. G., Roy, A., Lazar, A. J., Lopez-Terrada, D. H., & Wang, W. L. (2017). USP6 activation in nodular fasciitis by promoter-swapping gene fusions. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 30(11), 1577–1588. https://doi.org/10.1038/modpathol.2017.78
- Sápi, Z., Lippai, Z., Papp, G., Hegyi, L., Sápi, J., Dezső, K., & Szuhai, K. (2021). Nodular fasciitis: a comprehensive, time-correlated investigation of 17 cases. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 34(12), 2192–2199. https://doi.org/10.1038/s41379-021-00883-x